- Over the years, a wide variety of cell lines and primary cells have been employed to investigate Helicobacter pylori–host cell interactions. These models have proven essential for understanding key aspects of H. pylori pathogenesis, including bacterial adhesion, CagA translocation, host signaling responses, and epithelial barrier disruption.
- Among the most widely used models are gastric epithelial cell lines, particularly the AGS cell line derived from human gastric adenocarcinoma. AGS cells are especially useful for studying CagA phosphorylation and downstream signaling, though they lack full epithelial polarization and E-cadherin expression. Other gastric carcinoma lines, such as MKN-28, MKN-45, and NCI-N87, offer varying degrees of differentiation and polarization. For example, NCI-N87 forms tight junctions and polarized monolayers, making it more suitable for investigating barrier integrity and junctional protein localization during H. pylori infection.
- In recent years, primary gastric epithelial cells and human gastric organoids have gained popularity for their physiological relevance. These advanced models more accurately replicate the architecture, cellular diversity, and polarity of the native gastric epithelium, enabling more in-depth studies of long-term infection, epithelial regeneration, and host-pathogen interactions in a near-native context.
- Non-gastric polarized epithelial cell lines such as MDCK (Madin-Darby Canine Kidney), Caco-2, and T84 cells have also been used extensively. These models are particularly valuable for analyzing tight junction dynamics, epithelial polarity, and interactions involving scaffolding proteins like ZO-1 and polarity regulators such as PAR1b. While these cells are not of gastric origin, their ability to form polarized monolayers makes them useful for dissecting the mechanisms of H. pylori-induced epithelial dysfunction.
- Although H. pylori primarily colonizes the gastric epithelium, endothelial cells like HUVECs (human umbilical vein endothelial cells) and HMEC-1 (human microvascular endothelial cells) have occasionally been used in vitro. These models are typically employed to explore the systemic inflammatory consequences of infection or to examine the effects of bacterial products like VacA or lipopolysaccharides, rather than direct bacterial adhesion or CagA injection. Notably, there is limited to no evidence that H. pylori injects CagA into endothelial cells.
- In addition, immune cell models such as THP-1 monocytes, RAW264.7 macrophages, and primary dendritic cells or PBMCs are often used to study innate immune responses to H. pylori. While these cells do not support CagA translocation, they are valuable for understanding cytokine induction, inflammasome activation, and the broader immunomodulatory effects of H. pylori.
- Finally, 3D human gastric organoids and air-liquid interface cultures are emerging as state-of-the-art systems for modeling H. pylori infection. These models preserve tissue polarity, mucus production, and the presence of stem cell niches, offering an unparalleled platform for studying long-term colonization, host-pathogen interactions, and the development of precancerous changes in response to chronic infection.
